Citations

Study Design: Retrospective review. Objective: The purpose of this study was to investigate the surgical outcomes in a cohort of patients with severe preoperative axial neck pain undergoing laminoplasty for cervical spondylotic myelopathy (CSM). Summary of Background Data: No study has investigated whether patients with severe axial symptoms may achieve satisfactory neck pain and disability outcomes after laminoplasty. Methods: We performed a retrospective review of 91 patients undergoing C4-6 laminoplasty for CSM at a single academic institution between 2010 and 2021. Patient-reported outcome measures (PROMs), including Neck Disability Index (NDI), visual analog scale (VAS) Neck, and VAS Arm, were recorded preoperatively and at 6 months and 1 year postoperatively. Patients were stratified as having mild pain if VAS neck was 0–3, moderate pain if 4–6, and severe pain if 7–10. PROMs were then compared between subgroups at all the perioperative time points. Results: Both the moderate and severe neck pain subgroups demonstrated a substantial improvement in VAS neck from preoperative to 6 months postoperatively (−3.1±2.2 vs. −5.6±2.8, respectively; P<0.001), and these improvements were maintained at 1 year postoperatively. There was no difference in VAS neck between subgroups at either the 6-month or 1-year postoperative time points. Despite the substantially higher mean NDI in the moderate and severe neck pain subgroups preoperatively, there was no difference in NDI at 6 months or 1 year postoperatively (P=0.99). There were no differences between subgroups in the degree of cord compression, severity of multifidus sarcopenia, sagittal alignment, or complications. Conclusions: Patients with moderate and severe preoperative neck pain undergoing laminoplasty achieved equivalent PROMs at 6 months and 1 year as patients with mild preoperative neck pain. The results of this study highlight the multifactorial nature of neck pain in these patients and indicate that severe axial symptoms are not an absolute contraindication to performing laminoplasty in well-aligned patients with CSM.

Abstract Purpose: The determinants of response or resistance to radioiodine (RAI) are unknown. We aimed to identify genomic and transcriptomic factors associated with structural responses to RAI treatment of metastatic thyroid cancer, which occur infrequently, and to test whether high MAPK pathway output was associated with RAI refractoriness. Experimental Design: Exceptional response to RAI was defined as reduction of tumor volume based on RECIST v1.1. We performed a retrospective case–control study of genomic and transcriptomic characteristics of exceptional responders (ER; n = 8) versus nonresponders (NR; n = 16) matched by histologic type and stage at presentation on a 1:2 ratio. Results: ER are enriched for mutations that activate MAPK through RAF dimerization (RAS, class 2 BRAF, RTK fusions), whereas NR are associated with BRAFV600E, which signals as a monomer and is unresponsive to negative feedback. ER have a lower MAPK transcriptional output and a higher thyroid differentiation score (TDS) than NR (P &lt; 0.05). NR are enriched for 1q-gain (P &lt; 0.05) and mutations of genes regulating mRNA splicing and the PI3K pathway. BRAFV600E tumors with 1q-gain have a lower TDS than BRAFV600E/1q-quiet tumors and transcriptomic signatures associated with metastatic propensity. Conclusions: ER tumors have a lower MAPK output and higher TDS than NR, whereas NR have a high frequency of BRAFV600E and 1q-gain. Molecular profiling of thyroid cancers and further functional validation of the key findings discriminating ER from NR may help predict response to RAI therapy.

AbstractObjectivesTo create an otolaryngology‐specific needs assessment tool for short‐term global surgical trips and to describe our findings from its implementation.MethodsSurveys 1 and 2 were developed based on a literature review and disseminated to Low‐Middle Income (LMIC) hosting institutions in Kenya and Ethiopia and to High‐Income surgical trip participants (HIC), respectively. Respondents were otolaryngologists identified online, through professional organizations, and by word‐of‐mouth, who had participated in a surgical trip of <4 weeks.ResultsHIC and LMIC respondents shared similar goals of expanding host surgical skills through education and training while building sustainable partnerships. Discrepancies were identified between LMIC desired surgical skills and supply needs and HIC current practices. Microvascular reconstruction (17.6%), advanced otologic surgery (17.6%), and FESS (14.7%) were most desired skills and high‐demand equipment needs were FESS sets (89%), endoscopes (78%), and surgical drills (56%). Frequently taught techniques included advanced otologic surgery (36.6%), congenital anomaly surgery (14.6%), and FESS (14.6%) with the largest gap between LMIC‐need and HIC‐offerings being in microvascular reconstruction (17.6% vs. 0%). We also highlight the discrepancy in expectations of responsibility for trip logistics, research, and patient follow‐up.ConclusionWe created and implemented the first otolaryngology‐specific needs assessment tool in the literature. With its implementation in Ethiopia and Kenya, we were able to identify unmet needs as well as attitudes and perceptions of LMIC and HIC participants. This tool may be adapted and utilized to assess specific needs, resources, and goals of both host and visiting teams to facilitate successful global partnerships.Level of EvidenceLevel VI.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visitNCCN.org.

Abstract Context Metastatic pheochromocytomas and paragangliomas (mPPGL) are rare vascular neuroendocrine tumors that highly express vascular growth factors. Systemic treatment options in cases of unresectable multisite disease are limited. Multikinase inhibitors that inhibit angiogenesis, such as lenvatinib, have proven effective in several other malignancies, and may be a viable option for mPPGL. Objective We aimed to evaluate the efficacy of lenvatinib as salvage therapy in mPPGLs. Methods This was a retrospective analysis of mPPGL patients ≥ 18 years of age who received lenvatinib from 2015 to 2020 at a tertiary referral center. Patients were started on lenvatinib 20 mg daily and dose was adjusted according to tolerance or disease progression. Results Eleven patients were included. Median treatment duration was 14.7 months (95% CI, 2.3-NE). Treatment was discontinued due to disease progression, adverse events, or death. Overall survival at 12 months was 80.8% (95% CI, 42.3-94.9%) but its median was not reached. Median progression-free survival was 14.7 months (95% CI, 1.7-NE). Among the 8 patients with measurable disease, overall response rate was 63%, as 5/8 experienced a partial response and 3/8 had stable disease. Worsening hypertension and anemia were the most common adverse events. Conclusion Lenvatinib may be a viable treatment option for mPPGL, although at the potential risk of worsening hypertension. Larger, multicenter studies are needed to better characterize treatment efficacy.

AbstractBackgroundThe development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence‐based statement on the definition of advanced thyroid cancer and its targeted systemic treatment.MethodsAn expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel.ResultsA review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided.ConclusionsWith the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted.

Immune checkpoint inhibitors (ICIs) can cause pituitary dysfunction due to hypophysitis. We aimed to characterize ICI-induced hypophysitis and examine its association with overall survival in this single-center retrospective cohort study of adult patients with cancer who received an ICI from January 1, 2012 through December 31, 2016. A total of 896 patients were identified who received ipilimumab alone (n=120); ipilimumab and nivolumab (n=50); ipilimumab before or after pembrolizumab (n=70); pembrolizumab alone (n=406); and nivolumab alone (n=250). Twenty-six patients (2.9%) developed hypophysitis after a median of 2.3 months. Median age at the start of ICI was 57.9 years and 54% were men. Hypophysitis occurred in 7.9% of patients receiving ipilimumab alone or in combination or sequence with a programmed cell death protein 1 inhibitor; 1.7% after pembrolizumab alone, never after nivolumab alone. Secondary adrenal insufficiency occurred in all hypophysitis cases. Use of ipilimumab alone or in combination was associated with pituitary enlargement on imaging and mass effects more frequently than pembrolizumab alone. Occurrence of hypophysitis was associated with improved overall survival by univariate analysis (median 50.7 vs 16.5 months; p=0.015) but this association was not observed in multivariable landmark survival analysis (HR for mortality 0.75; 95% CI 0.38 to 1.30; p=0.34) after adjusting for age, sex and malignancy type. To conclude, hypophysitis occurred most frequently after ipilimumab and manifested as anterior hypopituitarism affecting the corticotrophs more commonly than thyrotrophs and gonadotrophs. Mass effects and pituitary enlargement occurred more frequently in ipilimumab-induced hypophysitis. The association of hypophysitis with overall survival needs further investigation.

Study Design Retrospective cohort study Objective Substantial variability in both the measurement and classification of subsidence limits the strength of conclusions that can be drawn from previous studies. The purpose of this study was to precisely characterize patterns of cervical cage subsidence utilizing computed tomography (CT) scans, determine risk factors for cervical cage subsidence, and investigate the impact of subsidence on pseudarthrosis rates. Methods We performed a retrospective review of patients who underwent one- to three-levels of anterior cervical discectomy and fusion (ACDF) utilizing titanium interbodies with anterior plating between the years 2018 and 2020. Subsidence measurements were performed by two independent reviewers on CT scans obtained 6 months postoperatively. Subsidence was then classified as mild if subsidence into the inferior and superior endplate were both ≤2 mm, moderate if the worst subsidence into the inferior or superior endplate was between 2 to 4 mm, or severe if the worst subsidence into the inferior or superior endplate was ≥4 mm. Results A total of 51 patients (100 levels) were included in this study. A total of 48 levels demonstrated mild subsidence (≤2 mm), 38 demonstrated moderate subsidence (2-4 mm), and 14 demonstrated severe subsidence (≥4 mm). Risk factors for severe subsidence included male gender, multilevel constructs, greater mean vertebral height loss, increased cage height, lower Taillard index, and lower screw tip to vertebral body height ratio. Severe subsidence was not associated with an increased rate of pseudarthrosis. Conclusion Following ACDF with titanium cervical cages, subsidence is an anticipated postoperative occurrence and is not associated with an increased risk of pseudarthrosis.

Purpose of review Our goal is to review pertinent data evaluating the association between immune checkpoint inhibitor (ICI)-induced endocrine dysfunction and survival in cancer patients as well as to understand the potential molecular links between these. Recent findings ICIs have revolutionized cancer therapy but have also led to multiple immune-related adverse events (irAEs). Studies have demonstrated a link between the development of irAEs and improved survival, suggesting that ICI-induced antitumor immunity and autoimmunity are coupled. Thyroid irAEs are most frequently and strongly associated with improved survival, particularly in the context of overt thyroid dysfunction. Other endocrine irAEs, such as hypophysitis and diabetes are quite rare wherein the treatment approach or the disease process itself may mitigate improvement in survival. Preclinical and translational data indicate a role for CD4+ T cells, regulatory T cells and/or cytokines mediating irAEs, including thyroiditis. Summary The development of irAEs is associated with improved tumor responses and survival in cancer patients. Thyroid irAEs, alone or in combination with other irAEs, are most strongly associated with improved outcomes. Biomarkers of response to ICIs are lacking, despite well-characterized pathologic and genomic susceptibilities predicting ICI efficacy. Early detection of thyroid irAEs may identify patients most likely to have durable antitumor response to ICIs. Although irAEs and antitumor immunity appear ‘coupled’, translational studies indicate the potential for their ‘uncoupling’, which could enable antitumor efficacy with greater safety margins.